JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: Implications for viral latency

The human polyomavirus JC virus (JCV) infects myelin-producing cells in the central nervous system, resulting in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently in immunosuppressed individuals, with the highest incidence in human immunodeficiency type I-infected patients, ranging between 4 and 6% of all AIDS cases, Although JCV targets a highly specialized cell in the central nervous system, infection is widespread, dth more than 80% of the human population worldwide demonstrating serum antibodies. A number of clinical and laboratory studies have now linked the pathogenesis of PML with JCV infection in lymphoid cells. For example, JCV-infected lymphocytes have been suggested as possible carriers of virus to the brain following reactivation of a latent infection in lymphoid tissues. To further define the cellular tropism associated with JCV, we have attempted to infect immune system cells, including CD34(+) hematopoietic progenitor cells derived from human fetal liver, primary human B lymphocytes, and human tonsillar stromal cells, Our results demonstrate that these cell types as well as a CD34(+) human cell line, KG-1a, are susceptible to JCV infection, JCV cannot, however, infect KG-1, a CD34(+) cell line which differentiates into a macrophage-like cell when treated with phorbol esters, In addition, peripheral blood B lymphocytes isolated by how cytometry from a PML patient demonstrate JCV infection. These results provide direct evidence that JCV is not strictly neurotropic hut can infect CD34(+) hematopoietic progenitor cells and those cells which have differentiated into a lymphocytic, but not monocytic, lineage.